Metabolic Remodelling in the Mouse Embryo and Placenta at Mid-Gestation

The metabolic landscape of the post-implantation mouse embryo and its associated placenta remains incompletely characterised. Here, we performed untargeted LC–MS-based metabolomics on mouse embryos from E9.5 to E13.5 and on placentas from E10.5 to E12.5, and integrated these data with a published single-cell transcriptomic atlas of the same developmental window. We found that the embryonic metabolome undergoes progressive remodelling, with the most pronounced changes occurring around E11.5. By combining time-course analysis, WGCNA-based network prioritisation, and embryo–placenta comparison, we identified 56 core metabolites that increased coordinately in both tissues during this period. Single-cell analysis revealed that the definitive erythroid lineage was enriched for nicotinate and nicotinamide metabolism, with progressive upregulation of the NAD+ biosynthetic enzyme Nmnat2 during erythroid maturation. Correspondingly, niacinamide, NAD, and 1-methylnicotinamide increased in the embryo from E10.5 to E13.5. Regulon analysis showed that haematopoiesis-related transcriptional programmes, including Spi1 and Gfi1, correlated with development-associated metabolic modules. Together, our data provide a stage-resolved metabolomic resource and identify candidate metabolites that may support embryo growth in vitro.